Galanthamine (and its derivatives) are useful compounds for the treatment of Alzheimer's disease and related illnesses. Currently galanthamine, nor-galanthamine and the oxidised precursors thereof, narwedine and nor-narwedine, are usually obtained by extraction from particular types of bulbs, such as daffodils or snowdrops. The yields of these extractive procedures are extremely low, resulting in product(s) which are expensive and in short supply.
Studies have shown that the biosynthesis of such compounds probably proceeds by a pathway similar to that shown in Scheme 1 below, where the key step is an oxidative cyclisation. These studies have also indicated that when the cyclisation precursor lacks a methyl group on the amine nitrogen (i.e. R.dbd.H) the biosynthesis to narwedine and galanthamine is disfavoured, and instead proceeds down other pathways, e.g. to pyrrolo(de)phenanthridine and ethanophenanthridine alkaloids (see Barton and Kirby, J. Chem. Soc. (1961) 806 and Fuganti et al, Tetrahedron Lett. (1974) 2261).